Authors: Rexhep Rexhepaj Anand Rotte Shuchen Gu Diana Michael Venkanna Pasham Kan Wang Daniela S Kempe Teresa F Ackermann Björn Brücher Falko Fend Michael Föller Florian Lang
Publish Date: 2011/03/11
Volume: 461, Issue: 5, Pages: 527-536
Abstract
Loss of function mutations of the tumor suppressor gene adenomatous polyposis coli APC underly the familial adenomatous polyposis Mice carrying an inactivating mutation in the apc gene apc Min/+ similarly develop intestinal polyposis APC is effective at least in part by degrading βcatenin and lack of APC leads to markedly enhanced cellular βcatenin levels βCatenin has most recently been shown to upregulate the Na+/K+ ATPase The present study thus explored the possibility that APC could influence intestinal transport The abundance and localization of βcatenin were determined utilizing Western blotting and confocal microscopy the activity of the electrogenic glucose carrier SGLT1 was estimated from the glucoseinduced current in jejunal segments utilizing Ussing chamber experiments and the Na+/H+ exchanger NHE3 activity from Na+dependent realkalinization of cytosolic pH ΔpHi following an ammonium pulse employing BCECF fluorescence As a result βcatenin abundance in intestinal tissue was significantly higher in apc Min/+ mice than in wildtype mice apc +/+ The βcatenin protein was localized in the basolateral membrane Both the glucoseinduced current and ΔpHi were significantly higher in apc Min/+ mice than in apc +/+ mice In conclusion intestinal electrogenic transport of glucose and intestinal Na+/H+ exchanger activity are both significantly enhanced in apc Min/+ mice pointing to a role of APC in the regulation of epithelial transport
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